It has been established that disuse results in greater neuromuscular detriment among the aged than among young adults. This presents a compounded risk to the aged since not only are they more likely to suffer from maladies and afflictions that result in muscle unloading (disuse) than the young, but they also suffer more remodeling of the neuromuscular system consequent to that disuse. The overall goal of the proposed project is to determine the efficacy of "pre-habilitation" - physical activity prior to unloading - in moderating the effects of disuse related alteration of the neuromuscular system. Both young adult and aged rats will either serve as untreated controls or be subjected to four weeks muscle unloading. Half of those animals exposed to unloading will participate in pre-habilitative exercise for two weeks prior to unloading. The specific aims of the research project are: 1) to determine the capacity of pre-habilitation to attenuate the negative adaptations observed in the neuromuscular system (muscle fibers, neuromuscular junctions) following unloading, 2) to ascertain the impact of aging on the efficacy of pre-habilitation, 3) to assess the relationship of NCAM expression - a synaptic regulatory molecule - in the morphological remodeling of the neuromuscular junction, and 4) to determine whether age-specific changes in the expression of Synpatotagmin - a protein essential to vesicular release during neurotransmission - are evident following unloading (with and without pre-habilitation). The data gathered will provide important new and useful insight regarding the potential of pre-habilitation to mitigate unloading induced disturbances in the neuromuscular system of young adults and the elderly, as well as the cellular mechanisms that may contribute to this palliative effect. [unreadable] [unreadable] [unreadable]